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Case Western Reserve University

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    3487 research outputs found

    A Planetary Imagination: Responses to Chakrabarty’s Socio-Natural Historiography, Editorial Introduction

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    Dipesh Chakrabarty’s 2009 essay in Critical Inquiry, “The Climate of History: Four Theses” sent tremors through the environmentally aware humanities in the 2010s. Last year, he published the book that brought that essay forward into the present, The Climate of History in a Planetary Age. It’s no overstatement to think of this book as having clanged the bell for a new normal in the humanities and social sciences when it comes to telling the story of ourselves, that is, when it comes to human history. Responsible history should today be geological even when recounting the human record. Chakrabarty raised a series of open-ended, difficult questions about a range of core concerns in the humanities and social sciences from how we can understand ourselves and society to how we ought to think about political economy and morality. How should these concerns be reconsidered – and their study reorganized – given the rupture of the Earth system sciences – and more generally the “planetary” – into their domains

    PUM1 Mediates the Posttranscriptional Regulation of Human Fetal Hemoglobin

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    The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its posttranscriptional regulation is poorly understood. Here, we identify Pumilo 1 (PUM1), an RNA-binding protein with no previously reported functions in erythropoiesis, as a direct posttranscriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin (HBG1) mRNA stability and translational efficiency, which culminates in reduced γ-globin protein levels. Knockdown of PUM1 leads to a robust increase in fetal hemoglobin (∼22% HbF) without affecting β-globin levels in human erythroid cells. Importantly, targeting PUM1 does not limit the progression of erythropoiesis, which provides a potentially safe and effective treatment strategy for sickle cell anemia and β-thalassemia. In support of this idea, we report elevated levels of HbF in the absence of anemia in an individual with a novel heterozygous PUM1 mutation in the RNA-binding domain (p.(His1090Profs∗16); c.3267_3270delTCAC), which suggests that PUM1-mediated posttranscriptional regulation is a critical player during human hemoglobin switching

    Vitrimerization of Rigid Thermoset Polyurethane Foams: A Mechanochemical Method to Recycle and Reprocess Thermosets

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    Polyurethane (PU) thermosets are extensively used in different applications and recycling the large amount of PU thermoset waste remains a universal challenge. Recycling the thermoset waste through vitrimerization is a feasible, cost-effective, and environmental-friendly approach. In this work, triazabicyclodecene (TBD) is used as organocatalyst in the vitrimerization process to recycle and reprocess thermoset rigid polyurethane foams. The results show that the permanent crosslinked structure of the PU thermoset foam is converted to a dynamic network upon vitrimerization. The vitrimerized network can rapidly relax the stress in 10 s at temperatures as low as 120°C. The topology rearrangement happens through the carbamate exchange reaction, mainly via a dissociative mechanism. The vitrimerized network retains high mechanical strength with Young\u27s Modulus of 2.7 GPa and tensile strength of 76.4 MPa and can be reprocessed for a second time without addition of extra catalyst and without loss in mechanical properties. The vitrimerized network can also be foamed by applying small pressure at high temperatures

    A Theory of City Biogeography and the Origin of Urban Species

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    Many of the choices humans make with regard to infrastructure, urban planning and other phenomena have impacts that will last thousands of years. This can readily be seen in modern cities in which contemporary streets run along street grids that were laid out thousands of years prior or even in which ancient viaducts still play a role. However, rarely do evolutionary biologists explicitly consider the future of life likely to be associated with the decisions we are making today. Here, we consider the evolutionary future of species in cities with a focus on the origin of lineages and species. We do so by adjusting evolutionary predictions from the theory of island biogeography so as to correspond to the unique features of cities as islands. Specifically, the species endemic to cities tend to be associated with the gray habitats in cities. Those habitats tend to be dominated by human bodies, pet bodies and stored food. It is among such species where the origin of new lineages is most likely, although most research on evolution in cities has focused on green habitats. We conclude by considering a range of scenarios for the far future and their implications for the origin of lineages and species

    Omicron Infection Milder in Nursing Home Residents

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    Social Determinants of Health and Child Maltreatment Prevention: The Family Success Network Pilot

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    Child maltreatment is a highly prevalent public health concern that contributes to morbidity and mortality in childhood and short- and long-term health consequences that persist into adulthood. Past research suggests that social determinants of health such as socioeconomic status and intergenerational trauma are highly correlated with child maltreatment. With support from the U.S. Children’s Bureau, the Ohio Children’s Trust Fund is currently piloting the Family Success Network, a primary child maltreatment prevention strategy in Northeast Ohio that seeks to address these social determinants through pillars of service that include family coaching, financial assistance, financial education, parenting education, and basic life skills training. This study highlights the initial development phase of a pilot study. Plans for in-depth process and outcome evaluations are discussed. The project seeks to improve family functioning and reduce child protective services involvement and foster care entry in an economically disadvantaged region

    The Planetary Sublime Part II of The Problem of an Unloving World

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    This essay interprets Dipesh Chakrabarty’s The Climate of History in a Planetary Age in light of the European tradition of thought about the sublime. The first half of the essay stages Chakrabarty’s historiography within that tradition focusing on a critical understanding of Kant. Then, the essay considers how the trace of the sublime in Chakrabarty’s approach to planetary history is interpretable as a form of social alienation. That argument draws on the critical theory of Steven Vogel and decolonial critique. Finally, the essay considers the moods of protest as non-alienated responses to the planetary bypassing the coloniality of the sublime

    Consensus Embedding for Multiple Networks: Computation and Applications

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    Machine learning applications on large-scale network-structured data commonly encode network information in the form of node embeddings. Network embedding algorithms map the nodes into a low-dimensional space such that the nodes that are “similar” with respect to network topology are also close to each other in the embedding space. Real-world networks often have multiple versions or can be “multiplex” with multiple types of edges with different semantics. For such networks, computation of Consensus Embeddings based on the node embeddings of individual versions can be useful for various reasons, including privacy, efficiency, and effectiveness of analyses. Here, we systematically investigate the performance of three dimensionality reduction methods in computing consensus embeddings on networks with multiple versions: singular value decomposition, variational auto-encoders, and canonical correlation analysis (CCA). Our results show that (i) CCA outperforms other dimensionality reduction methods in computing concensus embeddings, (ii) in the context of link prediction, consensus embeddings can be used to make predictions with accuracy close to that provided by embeddings of integrated networks, and (iii) consensus embeddings can be used to improve the efficiency of combinatorial link prediction queries on multiple networks by multiple orders of magnitude

    The Impact of Obesity and Adipokines on Breast and Gynecologic Malignancies

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    The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer-related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat-secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we now know that additional adipokines can impact tumorigenesis. A deeper understanding of the adipokine-activated signaling in cancer may identify new treatment strategies irrespective of obesity. Moreover, adipokines may serve as disease biomarkers, harnessing the potential of obesity-associated factors to serve as indicators of treatment response and disease prognosis. As studies investigating obesity and women\u27s cancers continue to expand, it has become evident that breast, ovarian, and uterine cancers are distinctly impacted by adipokines. While complex, these distinct interactions may provide insight into cancer progression in these organs and new opportunities for targeted therapies. This review aims to organize and present the literature from the last 5 years investigating the mechanisms and implications of adipokine signaling in breast, endometrial, and ovarian cancers with a special focus on leptin and adiponectin

    Moral Status and the Oversight of Research Involving Chimeric Animals

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    The use of nonhuman animals in research has long been a source of bioethical and scientific debate. We consider the oversight and use of nonhuman animals in chimeric research. We conducted interviews with twelve members of embryonic stem cell research oversight committees, nine members of institutional animal care and use committees, and fourteen scientists involved in human–nonhuman-animal chimeric research in different areas of the United States. Interviews addressed animal welfare and conceptual issues associated with moral status and humanization of nonhuman animals that contain human cells. Our findings suggest that concepts of enhanced moral status and consciousness are not very useful in human–nonhuman-animal chimeric research in part because their meanings are not easily defined, which presents challenges to applying the concepts in research. Instead, scientists and oversight committee members we interviewed seemed to rely on standard assessments of changes in animal welfare when focusing on the ethics of human-animal chimeric research

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